Genetic Analysis Using Targeted Subsets for High-GC Sequencing
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Solution Overview
Problem
Current whole genome and exome sequencing methods are costly and fail to capture biomedically important variants, particularly in regions with high CG content and repetitive elements, and do not provide adequate sequencing of non-exomic and exomic regions.
Innovation Solution
A method involving the production of two or more subsets of nucleic acid molecules with differing features such as genomic regions, GC content, and molecular size, followed by separate assays and subsequent combination of results using a computer processor to analyze the nucleic acid sample, including the use of capture probes and complementary nucleic acid libraries.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If whole genome and exome sequencing using standard sequencing methods are performed, then sequencing coverage is obtained, but sequencing sensitivity and accuracy are insufficient particularly in high GC content regions and repetitive elements
Solution Approach 1:
The patent divides the genome into multiple subsets based on different characteristics (high GC content regions, repetitive elements, standard regions). Each subset is processed separately with optimized protocols, allowing tailored sequencing approaches for different genomic regions. This segmentation enables improved sensitivity and accuracy by addressing the specific challenges of each region type rather than using a uniform approach.
Solution Approach 2:
The patent applies different sequencing protocols and enrichment strategies to different genomic regions. For example, specialized protocols are used for high GC content regions and repetitive elements, while standard protocols are used for常规 regions. This local quality approach ensures that each region is sequenced with the most appropriate method, improving overall measurement precision and reliability.
2Measurement precision
If multiple subsets of nucleic acid molecules are produced and analyzed separately, then sequencing sensitivity improves by 4-20%, but device complexity and processing time increase
Solution Approach 1:
The patent combines multiple sequencing results from different subsets and protocols into a unified analysis. By merging the data from high GC region sequencing, repetitive element sequencing, and standard region sequencing, the system achieves improved sensitivity while managing complexity through integrated data processing and combination strategies.
Solution Approach 2:
The patent develops a multi-functional sequencing system that can handle different types of genomic regions and protocols through a unified platform. The system is designed to process multiple subset types and combine their results, making the device versatile and reducing the need for separate specialized systems for each genome region type.
3Reliability
If specialized sequencing protocols are developed for different genomic regions, then sequencing accuracy in high GC content and repetitive regions improves, but cost and method complexity increase
Solution Approach 1:
The patent segments the genome into regions requiring specialized protocols (high GC, repetitive elements) and regions that can use standard protocols. This selective approach ensures that expensive specialized protocols are applied only where necessary, improving accuracy in challenging regions while maintaining cost-effectiveness for the majority of the genome that can be sequenced using standard methods.
Data Source
AI summary
This disclosure provides systems and methods for sample processing and data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Some or all of a nucleic acid sample may be sequenced to provide sequence information, which may be stored or otherwise maintained in an electronic storage location. The sequence information may be analyzed with the aid of a computer processor, and the analyzed sequence information may be stored in an electronic storage location that may include a pool or collection of sequence information and analyzed sequence information generated from the nucleic acid sample. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample, for producing one or more libraries, and for producing biomedical reports. Methods and systems of the disclosure can aid in the diagnosis, monitoring, treatment, and prevention of one or more diseases and conditions.